Tocotrienol Affects Oxidative Stress, Cholesterol Homeostasis and the Amyloidogenic Pathway in Neuroblastoma Cells: Consequences for Alzheimer's Disease

Int J Mol Sci. 2016 Oct 29;17(11):1809. doi: 10.3390/ijms17111809.


One of the characteristics of Alzheimer´s disease (AD) is an increased amyloid load and an enhanced level of reactive oxidative species (ROS). Vitamin E has known beneficial neuroprotective effects, and previously, some studies suggested that vitamin E is associated with a reduced risk of AD due to its antioxidative properties. However, epidemiological studies and nutritional approaches of vitamin E treatment are controversial. Here, we investigate the effect of α-tocotrienol, which belongs to the group of vitamin E, on AD-relevant processes in neuronal cell lines. In line with the literature, α-tocotrienol reduced the ROS level in SH-SY5Y cells. In the presence of tocotrienols, cholesterol and cholesterol esters, which have been shown to be risk factors in AD, were decreased. Besides the unambiguous positive effects of tocotrienol, amyloid-β (Aβ) levels were increased accompanied by an increase in the activity of enzymes responsible for Aβ production. Proteins and gene expression of the secretases and their components remained unchanged, whereas tocotrienol accelerates enzyme activity in cell-free assays. Besides enhanced Aβ production, tocotrienols inhibited Aβ degradation in neuro 2a (N2a)-cells. Our results might help to understand the controversial findings of vitamin E studies and demonstrate that besides the known positive neuroprotective properties, tocotrienols also have negative characteristics with respect to AD.

Keywords: Alzheimer´s disease; Aβ degradation; amyloid-β; tocopherol; tocotrienol; vitamin E; β-secretase; γ-secretase.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid Precursor Protein Secretases / biosynthesis
  • Amyloid beta-Peptides / metabolism*
  • Antioxidants / administration & dosage
  • Cell Line
  • Cholesterol / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Tocotrienols / administration & dosage
  • Vitamin E / administration & dosage


  • Amyloid beta-Peptides
  • Antioxidants
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Tocotrienols
  • Vitamin E
  • Cholesterol
  • Amyloid Precursor Protein Secretases